Behavioral and biological research on drug abuse will be conducted in multidisciplinary inpatient clinical studies of heroin addicts and polydrug users. Goals of the proposed research on narcotics abuse include evaluation of three new pharmacotherapies: (1) Non-narcotic polypeptide and steroid hormones with no known addiction liability; (2) Buprenorphine, a new partial agonist-antagonist; (3) Naltrexone, a long-active narcotic antagonist. Effects of these compounds on heroin self-administration and its subjective consequences will be evaluated in behavioral studies. Biological studies include: (1) examination of the effects of heroin and antagonists on pituitary-gonadal hormones and of covariance of tolerance and physical dependence on opiates with neuroendocrine function; (2) development and evaluation of a new measure of narcotic addiction liability which can be used safely in both man and animals; (3) study of basic mechanisms of action of opiate agonists and antagonists on hypothalamic-pituitary-gonadal hormones in human males. Behavioral studies of polydrug use propose to examine: (1) the effects of concurrent availability of marihuana and alcohol on patterns of drug acquisition and use; (2) subjective consequences of concurrent alcohol plus marihuana use, as contrasted to single drug use; (3) the effects of concurrent use of heroin, alcohol and marihuana on cigarette smoking. Behavioral and pharmacological factors which influence drug use patterns will be explored. Findings from clinical studies proposed should contribute to improved drug abuse treatment and prevention strategies, as well as to a better understanding of the behavioral an biological effects of drugs, and how these influence the maintenance of drug self-administration in man.